1. Field of the Invention
The present invention relates to an ophthalmic composition comprising a substance for regulating the rhythm of sleep, and a method for regulating the rhythm of sleep by the instillation of a medicament comprising the composition to the eye.
2. Description of the Related Art
Synthetic sleeping drugs have been used to correct the disorder in the rhythm of sleep. A synthetic sleeping drug is administered, if necessary, for example, to those suffered from a so-called jet lag after an overseas trip, a deteriorated physical condition due to three-shift work, nycterine poriomania due to senile dementia, and insomnia due to stress. However, since an excessive dose of some of the synthetic sleeping drugs can cause the death of a taker, close attention must be paid to their administration.
Such synthetic sleeping drugs are divided into two types: a barbiturate type and a non-barbiturate type. The barbiturate type sleeping drugs have a strong effect and thus are highly dangerous. The non-barbiturate type sleeping drugs have relatively moderate effects.
Among such non-barbiturate type sleeping drugs, benzodiazepine type sleeping drugs such as Halcion (trade name) are regarded to be comparatively safe and are widely utilized clinically these days. But it is known that these drugs can cause anterograde amnesia. It is unknown how the amnesia occurs, but the cause is presumed to be as follows. Sleep is generally divided into two types on the basis of the characteristics thereof: Non-REM sleep (slow wave sleep) and REM sleep (paradoxical sleep). The physiological meanings of the two types have not been fully understood as yet, but it is known that a rat that has been experimentally deprived of REM sleep, that is, a REM sleep deprivation rat, suffers from memory defect for a long period of time. Therefore, REM sleep is definitely concerned with memory fixing. The benzodiazepine type sleeping drugs lower the function of the brain and shorten the duration of REM sleep, and so they can induce anterograde amnesia. Therefore, such benzodiazepine type sleeping drugs are not suitable for patients with senile dementia who can easily fall into amnesia or other defects of memory and for students preparing themselves for an examination who should maintain their memory as clearly as possible.
Since the synthetic sleeping drugs are somewhat dangerous in this manner, it is impossible to obtain them without the prescription of a doctor, which causes inconvenience for those who are not under medical treatment.
On the other hand, sleep inducing substances derived from an organism have been reported as being different from the above described synthetic sleeping drugs. Substances derived from an organism herein mean substances existing in a body of an organism. Examples of such substances include those synthesized in the body of an organism and those from outside a body and utilized after intake for metabolism. It is known that these sleep inducing substances induce natural and physiological sleep without reducing the hours of REM sleep (Borbely et al., Physiol. Rev., 69: 605 (1989)). Such substances do not cause anterograde amnesia as the synthetic sleeping drugs do. Sleep inhibiting substances derived from an organism are also known, and there is no report of any habituation by using such sleep inhibiting substances over a long period of time.
Therefore, these sleep inducing substances and sleep inhibiting substances both derived from organisms (hereinafter referred to as the "sleep adjusting substances") are very useful in treating any disorder in the rhythm of sleep.
As an administration method of a sleeping drug, an oral administration or an injection is generally used, and the oral administration is preferred because it is simple. However, the sleep inducing or sleep inhibiting substances derived from organisms is significantly effective only when they are administered directly into a cerebral ventricle. There are a few reports that it was effective to administer them into an abdominal cavity. But the administration into the cerebral ventricle or abdominal cavity is neither convenient nor practical. As the oral administration of these substances, relief of jet lag by orally administering melatonin has been reported (Arendt et al., Br. Med. J., 292: 1170 (1986); and oral administration of tryptophan is known. In these cases, the oral administration is somewhat effective, but there is no report, except for the above, that the oral administration of the above described sleep adjusting substances derived from an organism is effective. This is because these substances have a disadvantage that they are easily metabolized in an organism and scarcely reach the region for adjusting the biological rhythm in the brain since they are derived from an organism. Therefore, it has been impossible to put these substances to practical use.